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Enhancers active in dopamine neurons are a primary link between genetic variation and neuropsychiatric disease.
Dong, Xianjun; Liao, Zhixiang; Gritsch, David; Hadzhiev, Yavor; Bai, Yunfei; Locascio, Joseph J; Guennewig, Boris; Liu, Ganqiang; Blauwendraat, Cornelis; Wang, Tao; Adler, Charles H; Hedreen, John C; Faull, Richard L M; Frosch, Matthew P; Nelson, Peter T; Rizzu, Patrizia; Cooper, Antony A; Heutink, Peter; Beach, Thomas G; Mattick, John S; Müller, Ferenc; Scherzer, Clemens R.
Afiliação
  • Dong X; Precision Neurology Program, Harvard Medical School and Brigham & Women's Hospital, Boston, MA, USA.
  • Liao Z; Center for Advanced Parkinson's Disease Research of Harvard Medical School and Brigham & Women's Hospital, Boston, MA, USA.
  • Gritsch D; Precision Neurology Program, Harvard Medical School and Brigham & Women's Hospital, Boston, MA, USA.
  • Hadzhiev Y; Center for Advanced Parkinson's Disease Research of Harvard Medical School and Brigham & Women's Hospital, Boston, MA, USA.
  • Bai Y; Precision Neurology Program, Harvard Medical School and Brigham & Women's Hospital, Boston, MA, USA.
  • Locascio JJ; Center for Advanced Parkinson's Disease Research of Harvard Medical School and Brigham & Women's Hospital, Boston, MA, USA.
  • Guennewig B; Institute of Cancer and Genomic Sciences, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK.
  • Liu G; Precision Neurology Program, Harvard Medical School and Brigham & Women's Hospital, Boston, MA, USA.
  • Blauwendraat C; State Key Laboratory of Bioelectronics, School of Biological Science and Medical Engineering, Southeast University, Nanjing, China.
  • Wang T; Precision Neurology Program, Harvard Medical School and Brigham & Women's Hospital, Boston, MA, USA.
  • Adler CH; Center for Advanced Parkinson's Disease Research of Harvard Medical School and Brigham & Women's Hospital, Boston, MA, USA.
  • Hedreen JC; Department of Neurology, Massachusetts General Hospital, Boston, MA, USA.
  • Faull RLM; Sydney Medical School, Brain and Mind Centre, The University of Sydney, Sydney, New South Wales, Australia.
  • Frosch MP; Division of Neuroscience, Garvan Institute of Medical Research, Sydney, New South Wales, Australia.
  • Nelson PT; St Vincent's Clinical School, UNSW Sydney, Sydney, New South Wales, Australia.
  • Rizzu P; Precision Neurology Program, Harvard Medical School and Brigham & Women's Hospital, Boston, MA, USA.
  • Cooper AA; Center for Advanced Parkinson's Disease Research of Harvard Medical School and Brigham & Women's Hospital, Boston, MA, USA.
  • Heutink P; German Center for Neurodegenerative Diseases (DZNE), Tübingen, Germany.
  • Beach TG; Precision Neurology Program, Harvard Medical School and Brigham & Women's Hospital, Boston, MA, USA.
  • Mattick JS; Center for Advanced Parkinson's Disease Research of Harvard Medical School and Brigham & Women's Hospital, Boston, MA, USA.
  • Müller F; Department of Neurology, Mayo Clinic, Scottsdale, AZ, USA.
  • Scherzer CR; Harvard Brain Tissue Resource Center, McLean Hospital, Harvard Medical School, Boston, MA, USA.
Nat Neurosci ; 21(10): 1482-1492, 2018 10.
Article em En | MEDLINE | ID: mdl-30224808
Enhancers function as DNA logic gates and may control specialized functions of billions of neurons. Here we show a tailored program of noncoding genome elements active in situ in physiologically distinct dopamine neurons of the human brain. We found 71,022 transcribed noncoding elements, many of which were consistent with active enhancers and with regulatory mechanisms in zebrafish and mouse brains. Genetic variants associated with schizophrenia, addiction, and Parkinson's disease were enriched in these elements. Expression quantitative trait locus analysis revealed that Parkinson's disease-associated variants on chromosome 17q21 cis-regulate the expression of an enhancer RNA in dopamine neurons. This study shows that enhancers in dopamine neurons link genetic variation to neuropsychiatric traits.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Variação Genética / Encéfalo / Locos de Características Quantitativas / Neurônios Dopaminérgicos / Transtornos Mentais Tipo de estudo: Diagnostic_studies Limite: Animals / Female / Humans / Male Idioma: En Revista: Nat Neurosci Assunto da revista: NEUROLOGIA Ano de publicação: 2018 Tipo de documento: Article País de afiliação: Estados Unidos
Texto completo
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Variação Genética / Encéfalo / Locos de Características Quantitativas / Neurônios Dopaminérgicos / Transtornos Mentais Tipo de estudo: Diagnostic_studies Limite: Animals / Female / Humans / Male Idioma: En Revista: Nat Neurosci Assunto da revista: NEUROLOGIA Ano de publicação: 2018 Tipo de documento: Article País de afiliação: Estados Unidos